Deferasirox (1) is an iron-chelator, which reduces iron overload in patients receiving long-term blood transfusions for conditions such as beta-thalassemia and other chronic anemia. It binds selectively with Fe3+ ions in a 2:1 ratio. Deferasirox is approved by FDA and marketed as Exjade®. Chemically deferasirox is 4-[3,5-Bis (2-hydroxyphenyl)-1H-1,2,4-triazol-1yl]-benzoic acid, having molecular formula C21H15N3O4, and the molecular weight 373.4.
U.S. Pat. No. 6,465,504 B1 discloses substituted 3,5-diphenyl-1,2,4-triazoles and their use as pharmaceutical metal chelators in which salicyloyl chloride (Formula-2) is reacted with salicylamide (Formula-3) at 170° C. to obtain 2-(2-hydroxyphenyl)benze[e][1,3]oxazin-4-one (Formula-4) as slightly yellow crystals having melting point 206-208° C., which is then reacted with 4-hydrazinobenzoic acid (Formula-5) in ethanol under reflux conditions to obtain 4-[3,5-Bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1yl]-benzoic acid (Deferasirox) as colorless crystals having melting point 264-265° C.

Upon the repetition of the disclosed procedure, deferasirox (1) was obtained as crystalline polymorphic form-I. However the obtained material does not meet the quality parameters such as chromatographic purity, residue on ignition, and appearance as per the ICH guidelines. Hence, a need for a more robust purification process of this crude deferasirox is inevitable to meet the quality parameters of the final API. In the reported procedures the condensation of salicyloyl chloride with salicylamide was conducted at 170° C., which is highly challenging and hazardous at commercial scales. This reaction at this combustible temperature also generates by-products such as uncyclised derivative; 2-hydroxy-N-(2-hydroxybenzoyl)benzamide compound (bis-salicylamide) of formula-6, which is difficult to remove from desired product. Though in the gram scale reactions the above said impurity is formed more than 10%, in the scale up reactions the formation of this impurity is formed about >20%. Hence, controlling the formation of this bis-salicylamide to minimum possible levels is essential.

Crystalline polymorphic form-I of deferasirox is disclosed in IPCOM000146862D, characterized by PXRD having 2⊖ values at about 13.2, 14.1, and 16.6±0.2 degrees. The characteristic 2⊖ values of Form-I is further elaborated as 6.6, 10.0, 10.6, 20.3, 23.1, 25.7, 26.2±0.2 degrees.
WO 2008/065123 discloses use and the process of novel polymorphs designated as Form-A, B, C, D and Sb. On the other hand, WO 2008/094617 reports the polymorphic forms of deferasirox designated as Form-II, Form-III, Form-IV and their conversion to most stable polymorph Form-I. An Indian Patent application 1924/CHE/2008 reports novel solvates of deferasirox and their conversion to deferasirox.
Hence there is a great need for commercially viable process with ease of operations for the preparation of deferasirox crystalline polymorphic form-I which meets the API quality parameters and ICH limits.